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The sensor properties of single-walled boron nitride nanotubes (BNNTs) towards acetone are studied by investigating the intermolecular interactions of acetone with a serials of pristine and doped BNNTs. Density-functional theory (DFT) with empirical dispersion corrected is adopted to explore the adsorption properties of acetone on the surface of BNNT. Results show that acetone binds strong to the surface of pristine BNNTs with small diameter and the adsorption energy decreases significantly as the tube diameter increases. The adsorption of acetone on serials of doped BNNTs (Al, Si, Cu, Co, Ni, Ga, and Ge) shows that the adsorption of acetone on BNNT can be strengthened by the doped impurity. With the analysis of charge density, density of states, molecular orbitals, and the noncovalent interaction index (NCI), the study shows that the sensitivity of BNNT-based chemical gas sensor towards acetone can be remarkable improved by introducing appropriate dopant. The study also reveals the potential application of BNNT as sensor for the detection of acetone molecule. [ABSTRACT FROM AUTHOR]

The carbon monoxide (CO) catalytic oxidation reaction is a model reaction which is important in serials of technical and industrial applications. In this study, density functional theory (DFT) is employed to explore the catalytic oxidation of CO on Pd-doped boron nitride nanotube (BNNT). The electronic structures and thermodynamic parameters of CO and O 2 , which are adsorbed on BNNT substrate with Pd embedded at the N- and B- vacancy, are examined in detail. It is revealed that the BNNT substrate with vacancy strongly stabilizes the Pd adatom. Benefit from the B vacancy defect, the Pd atom binds strongly with BNNT. The interaction energy of 3.74 eV is strong enough to prevent the aggregation of Pd atom. With B vacancy, Pd atom accepts extra electron from the substrate, causing O 2 to bind stronger than CO molecule. An additional charge is transferred to O 2 when CO and O 2 are co-adsorbed on the substrate. This additional charge thus strengthens the O 2 and CO adsorption and changes the electronic structure properties of the tube. Four proposed CO oxidation mechanisms (Eley–Rideal (ER), Langmuir–Hinshelwood (LH), termolecular Eley–Rideal (TER), and termolecular Langmuir–Hinshelwood (TLH)) are studied by calculating the reaction energy barriers along the minimum-energy pathway. It is found that a large reaction barrier exists in the rate-limiting step of the ER mechanism. It is then suggested that the most probable mechanisms for CO oxidation on Pd doped boron vacancy BNNT (Pd-Bv/BNNT) could be the LH mechanism and the new TER and TLH mechanisms under experimental circumstances. [ABSTRACT FROM AUTHOR]

The blood-spinal cord barrier (BSCB) plays important roles in the recovery of spinal cord injury (SCI), and caveolin-1 is essential for the integrity and permeability of barriers. Basic fibroblast growth factor (bFGF) is an important neuroprotective protein and contributes to the survival of neuronal cells. This study was designed to investigate whether bFGF is beneficial for the maintenance of junction proteins and the integrity of the BSCB to identify the relations with caveolin-1 regulation. We examined the integrity of the BSCB with Evans blue dye and fluorescein isothiocyanate-dextran extravasation, measured the junction proteins and matrix metalloproteinases, and evaluated the locomotor function recovery. Our data indicated that bFGF treatment improved the recovery of BSCB and functional locomotion in contusive SCI model rats, reduced the expression and activation of matrix metalloproteinase-9, and increased the expressions of caveolin-1 and junction proteins, including occludin, claudin-5, p120-catenin, and β-catenin. In the brain, in microvascular endothelial cells, bFGF treatment increased the levels of junction proteins, caveolin-1 small interfering RNA abolished the protective effect of bFGF under oxygen-glucose deprivation conditions, and the expression of fibroblast growth factor receptor 1 and co-localization with caveolin-1 decreased significantly, which could not be reversed by bFGF treatment. These findings provide a novel mechanism underlying the beneficial effects of bFGF on the BSCB and recovery of SCI, especially the regulation of caveolin-1. [ABSTRACT FROM AUTHOR]

Lipid nanoparticles with solid matrix have been given increasing attention due to their biodegradable status and ability to entrap a variety of biologically active compounds. In this study, new phospholipid-based gelatin nanoparticles encapsulating basic fibroblast growth factor (bFGF) were developed to target the brain via nasal administration. Treatment effects were assessed by quantifying rotational behavior, monoamine neurotransmitter levels and tyrosine hydroxylase expression in 6-hydroxydopamine induced hemiparkinsonian rats. The gelatin nanostructured lipid carriers (GNLs) were prepared by a water-in-water emulsion method and then freeze-dried. The GNLs possessed better profile than gelatin nanoparticles (GNs), with particle size 143±1.14nm and Zeta potential −38.2±1.2mV. The intranasal GNLs efficiently enriched exogenous bFGF in olfactory bulb and striatum without adverse impact on the integrity of nasal mucosa and showed obvious therapeutic effects on hemiparkinsonian rats. Thus, GNLs are attractive carriers for nose-to-brain drug delivery, especially for unstable macromolecular drugs such as bFGF. From the Clinical Editor: This team of authors reports the development of phospholipid-based gelatin nanoparticles encapsulating basic fibroblast growth factor to target the brain via intranasal administration. A rat model of hemiparkinsonism was applied demonstrating a good safety profile and an obvious therapeutic effect. [ABSTRACT FROM AUTHOR]

Abstract: After artificial hatching Locusta migratoria manilensis Meyen, the male adults were cultured in different temperature. By flow cytometry, DNA contents of apoptotic cells of germ cells were tested and analysed. The results showed that the apoptotic cells under different temperature always appeared in spermatogenesis of Locusta migratoria manilensis Meyen but arrived the peak in 45°C. The conclusion of the study showed that the 25°C was the best temperature of development and the 45°C was the worst temperature of development in spermatogenesis of Locusta migratoria manilensis Meyen. [Copyright &y& Elsevier]

Abstract: Objective: To investigate the protective effect of a mutant of acidic fibroblast growth factor (MaFGF) against cerebral ischaemia-reperfusion injury in rats. Methods: Sixty male Sprague–Dawley rats were randomly divided into six groups as follows: sham-operated group, untreated group, 20μg/kg, 40μg/kg and 80μg/kg MaFGF-treated groups and also the positive control group. Cerebral ischaemia-reperfusion injury was induced by middle cerebral artery occlusion (MCAO) for 2h followed by reperfusion for 24h. Different dose of MaFGF were infused intravenously at 1h after middle cerebral artery (MCA) occlusion. Nimodipine was used as positive control. The behaviour deficit score, brain-infarcted area, brain oedema degree, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were detected at 24h after reperfusion. Results: The results showed that MaFGF at the dose of 20μg/kg, 40μg/kg and 80μg/kg significantly alleviated brain injury. Compared to untreated group, the behaviour deficits were much less severe, the brain oedema alleviated obviously, the MDA contents decreased and SOD activity increased dramatically in MaFGF-treated groups respectively. The efficacy of MaFGF was similar to that of nimodipine. Conclusion: The results demonstrate that MaFGF has neuroprotective effect against brain injury resulting from focal ischaemia-reperfusion in Sprague–Dawley rats. [Copyright &y& Elsevier]

Abstract: Background: In our previous study, a mutant human acidic fibroblast growth factor without mitogenic action (nonmitogenic human acidic fibroblast growth factor) was created, and its protection from the cytotoxic effect of hydrogen peroxide treatment was confirmed in cultured cardiomyocytes. Methods: The present study was performed to further investigate whether genetically overexpressing nonmitogenic human acidic fibroblast growth factor in cardiomyocytes provides similar protection from the cytotoxic effect of hydrogen peroxide and whether in vivo administration of nonmitogenic human acidic fibroblast growth factor attenuates ischemia/reperfusion-induced cardiac dysfunction and tissue damage and protects the carotid sinus baroreceptor from alcohol-induced damage, as shown by a reduced response of blood pressure to short carotid artery occlusion. Results and conclusions: Cardiomyocytes transfected by nonmitogenic human acidic fibroblast growth factor, with significant increases in the cellular expression and secretion of nonmitogenic human acidic fibroblast growth factor into a culture medium, were resistant to hydrogen-peroxide-induced cytotoxicity, as measured by cell viability. Hearts isolated from rats pretreated with saline, human acidic fibroblast growth factor, or nonmitogenic human acidic fibroblast growth factor for 24 h were subjected to ischemia/reperfusion in the Langendorff system. Ischemia/reperfusion induced cardiac dysfunction in the saline group, but not in the group pretreated with human acidic fibroblast growth factor or nonmitogenic human acidic fibroblast growth factor. Ischemia/reperfusion also caused a release of the cardiac enzyme lactic dehydrogenase into—and an increase in lipid peroxide content in the efflux of—the hearts of saline-treated rats, but not in rats pretreated with human acidic fibroblast growth factor or nonmitogenic human acidic fibroblast growth factor. There was no difference in cardioprotective effects between human acidic fibroblast growth factor and nonmitogenic human acidic fibroblast growth factor. Furthermore, the protective effect of in-vivo-administered nonmitogenic acidic fibroblast growth factor on alcohol-induced damage to the carotid sinus baroreceptor, as shown by the reduced response of blood pressure to short carotid artery occlusion, was also observed. These results suggest that nonmitogenic human acidic fibroblast growth factor, similar to the native human acidic fibroblast growth factor, provides significant cardiovascular protection from oxidative damage in vitro and in vivo. [Copyright &y& Elsevier]

Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne virus that carries a high fatality rate of 12%–50%. In-depth understanding of the SFTSV-induced pathogenesis mechanism is critical for developing effective anti-SFTS therapeutics. Here, we report transcriptomic analysis of blood samples from SFTS patients. We observe a strong correlation between inflammatory responses and disease progression and fatal outcome. Quantitative proteomic analysis of SFTSV infection confirms the induction of inflammation and further reveals virus-induced mitochondrial dysfunction. Mechanistically, SFTSV infection triggers BCL2 antagonist/killer 1 (BAK) upregulation and BAK/BCL2-associated X (BAX) activation, leading to mitochondrial DNA (mtDNA) oxidization and subsequent cytosolic release. The cytosolic mtDNA binds and triggers NLRP3 inflammasome activation. Notably, the BAK expression level correlates with SFTS disease progression and fatal outcome. These findings provide insights into the clinical features and molecular underpinnings of severe SFTS, which may aid in patient care and therapeutic design, and may also be conserved during infection by other highly pathogenic viruses. • SFTSV induces mitochondrial damage triggering excessive inflammatory responses via NLRP3 • SFTSV induces BAK/BAX activation leading to cytosolic release of oxidized mtDNA • The cytosolic oxidized mtDNA binds and activates NLRP3 inflammasome • BAK expression level correlates with SFTS disease progression and fatal outcome Li et al. reveal that mitochondrial dysfunction induced by SFTSV infection triggers excessive inflammatory responses associated with SFTS disease progression and fatal outcome. Mechanistically, SFTSV infection induces BAK/BAX activation resulting in mtDNA oxidization and cytosolic release. The cytosolic oxidized mtDNA binds to and triggers NLRP3 inflammasome activation. [ABSTRACT FROM AUTHOR]

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with an increasing case number and extensive geographical expansion, raising concerns locally and globally; however, the description of its clinical features needs to be addressed by large studies. We aimed to determine all the clinical features of SFTS in a large population of patients in an endemic area.Methods: In this prospective observational study, data were collected on patients admitted to the People's Liberation Army Hospital in Xinyang, Henan Province, China, with laboratory-diagnosed SFTS. Demographic, clinical, laboratory, and treatment data were collected for each patient, and patients were followed up within 2 weeks after discharge or discontinuation of treatment. The association between each demographic, clinical, and laboratory variable with a fatal outcome was assessed. A clinical scoring model was designed for the early prediction of a fatal outcome, and the effect of treatment on outcome was analysed.Findings: Between April 1, 2011, and Oct 31, 2017, 2096 patients with laboratory-confirmed SFTS were admitted. Mean age at admission was 61·4 years (SD 12·2) and 1239 (59%) patients were female. The case fatality rate (CFR) was 16·2% (95% CI 14·6-17·8). A higher risk was associated with being male (unadjusted odds ratio [OR] 1·45, 95% CI 1·15-1·83; p=0·002), older age (for a 10-year increase, unadjusted OR 1·82, 95% CI 1·62-2·04; p<0·0001), longer delay in admission (for every extra day taken before admission to hospital, unadjusted OR 1·18, 1·12-1·24; p<0·0001), presence of diarrhoea (adjusted OR 1·44, 1·12-1·87; p=0·005) or dyspnoea (adjusted OR 8·35, 5·97-11·69; p<0·0001), and development of haemorrhagic signs (adjusted OR 2·79, 95% CI 2·18-3·57; p<0·0001) or neurological symptoms (adjusted OR 30·26, 21·39-42·81; p<0·0001). Laboratory variables that were associated with death included abnormal concentrations of lactate dehydrogenase, aspartate aminotransferase, and blood urea nitrogen, and abnormal neutrophil percentage, which together with age and neurological symptoms were combined in the clinical scoring system. A total score of more than 8 was the optimal threshold to predict risk of death for patients who were evaluated within 6 days after symptom onset (area under the curve 0·879, 95% CI 0·855-0·902). For all participants, viraemia was a strong predictor of fatal outcome (all p<0·0001). Ribavirin therapy was effective in reducing CFR from 6·25% (15 of 240 participants) to 1·16% (two of 173 participants), but only in patients with a viral load below 1×106 copies per mL (hazard ratio 9·72, 95% CI 1·30-72·87; p=0·027).Interpretation: The changing epidemiological features and high CFR of SFTS underscore the necessity of continued surveillance. Early prediction of fatal outcome can be attained by monitoring of clinical and laboratory data. Ribavirin should be applied early, with best results achieved before the viral load reaches 1 × 106 copies per mL.Funding: National Natural Science Foundation of China. [ABSTRACT FROM AUTHOR]

The complete mitochondrial genome (mitogenome) of Biston marginata (Lepidoptera: Geometridae) was determined and annotated. The circular genome is 15,470 bp long and it contains the entire set of 37 genes usually present in lepidopteran mitogenomes. The nucleotide composition of the genome is highly A + T biased, accounting for 81.20%, with a slightly positive AT skewness (0.028), indicating the occurrence of more As than Ts, as found in other Geometridae species. Except for cox1 gene starts with non-canonical initial codon CGA, all protein-coding genes start with ATN codon. Three of the 13 PCGs (protein coding gene) had an incomplete termination codon, T or TA, while the others terminated with TAA. All tRNA genes are predicted to fold into typical clover-leaf secondary structure, except for the trnS1 (AGN), in which the dihydrouridine (DHU) arm could not form a stable stem-loop structure. The A + T-rich region of 343 bp is comprised of non-repetitive sequences, but have several distinctive features, including the motif “ATAGA” followed by a 19 bp poly-T stretch, a microsatellite-like (TA) 7 element next to the ATTTA motif. The phylogenetic analyses support the view that the B. marginata is closely related to the Biston pantrinaria , and confirm that Biston marginata belongs to the family Geometridae. [ABSTRACT FROM AUTHOR]

Abstract: Multidrug resistance (MDR) is one of the major reasons for the failure of cancer chemotherapy. A newly reported liposome carrier, propylene glycol liposomes (EPI-PG-liposomes) were made to load epirubicin (EPI) which enhanced EPI absorption in MDR tumor cells to overcome the drug resistance. MDA-MB 435 and their mutant resistant (MDA-MB 435/ADR) cells were used to examine the cellular uptake and P-gp function in vitro for EPI-PG-liposomes by fluorescence microscopy and FCM, respectively. Mammary tumor model was also established to investigate the tumor growth inhibition and pharmacodynamics of EPI-PG-liposomes in vivo. Morphology evaluation showed that EPI-PG-liposomes had a homogeneous spherical shape with an average diameter of 182nm. Based on cell viability assay, fluorescent microscopy examination, and EPI uptake assay, EPI-PG-liposomes exhibited an effective growth inhibition not only in MDA-MB-435 cells, but also in MDA-MB 435/ADR cells. EPI-PG-liposomes have high permeability not only on tumor cell membrane, but also on cell nucleus membrane. P-gp function assay showed that the anticancer action of EPI-PG-liposomes was not related to P-gp efflux pump, suggesting that PG-liposomes would not affect the normal physiological functions of membrane proteins. EPI-PG-liposomes also showed a better antitumor efficacy compared to EPI solution alone. With high entrapment efficiency, spherical morphology and effective inhibition on MDR cancer cells, EPI-PG-liposomes may represent a better chemotherapeutic vectors for cancer targeted therapy. [Copyright &y& Elsevier]

Abstract: Characterization and anti-tumor activity of chemical conjugation of doxorubicin (DOX) in polymeric micelles were investigated. Polymeric micelles with chemical conjugation of doxorubicin (DOX-P) were prepared. Succinic anhydride activated pluronic F68 was first synthesized and the primary amine group in doxorubicin was conjugated to the terminal carboxyl of pluronic F68 via a amide. The resulting polymeric micelles in aqueous solution were characterized by measurement of size, ξ-potential, drug loading and critical micelle concentration. From characterization results, DOX-P micelles had superiorities over physically-loaded DOX micelles in loading efficiency, diameter and CMC value. From drug release experiment in vitro, DOX-P micelles reached a sustained release profile for DOX. The cytotoxic activity of the micelles against A549/DOX cells was greater than free DOX. Fluorescence microscope observation and flow cytometry analysis supported the enhanced cellular uptake of the micelles. From A549/DOX cells experiments, DOX-P micelles could enhance DOX anti-tumor activity and circumvent the multi-drug resistance (MDR) of A549/DOX cells. With low CMC value, high loading efficiency, nanometer diameter, good penetration ability and controlled release behaviour, DOX-P micelles might be developed as a new cancer targeted delivery system. [Copyright &y& Elsevier]

Abstract: A new series of complexes of a ligand 4′, 7, 8-trihydroxy-isoflavone with transition metal (zinc, copper, manganese, nickel, cobalt) and selenium have been synthesized and characterized with the aid of elemental analysis, IR, electron ionization mass spectrum (EI-MS) and 1H NMR spectrometric techniques. The compounds were evaluated for their in vitro antibacterial activities and antitumor properties. The metal complexes were found to be more active than the free ligand. Investigation on the interaction between the complexes and calf-thymus DNA (CT DNA) showed that the absorbance of CT DNA increased and the maximum peak (λmax =260nm) red-shifted, while the intensity of fluorescence spectra of Epstein-Bart DNA (EB-DNA) gradually weakened, which indicated that all of these metal complexes tightly combined with CT DNA. [Copyright &y& Elsevier]

Abstract: 11β-Hydroxysteroid dehydrogenase 2 (11β-HSD2) regulates active glucocorticoid access to glucocorticoid and mineralocorticoid receptors by metabolizing it to an inactive form. Perfluoroalkylated substances (PFASs) are man-made polyfluorinated compounds that are widely used and persistent in the environment. We tested the inhibitory potencies of four PFASs including perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexanesulfonate (PFHxS) and perfluorobutane sulfonate (PFBS) on human and rat 11β-HSD2. PFOS was a potent inhibitor of both human (IC50 =48nM) and rat (IC50 =293nM) 11β-HSD2 activities. The potencies for the inhibition of human and rat 11β-HSD2 activities were PFOS>PFOA>PFHxS>PFBS. PFASs showed competitive inhibition of both human and rat 11β-HSD2 activities. This observation indicates that PFOS is a potent endocrine disruptor for glucocorticoid metabolism. Article from the Special issue on Targeted Inhibitors. [Copyright &y& Elsevier]

Abstract: Perfluorooctane acid (PFOA) is classified as a persistent organic pollutant and as an endocrine disruptor. The mechanism by which PFOA causes reduced testosterone production in males is not known. We tested our hypothesis that PFOA interferes with Leydig cell steroidogenic enzymes by measuring its effect on 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase 3 (17β-HSD3) activities in rat testis microsomes and Leydig cells. The IC50s of PFOA and mode of inhibition were assayed. PFOA inhibited microsomal 3β-HSD with an IC50 of 53.2±25.9μM and 17β-HSD3 with an IC50 17.7±6.8μM. PFOA inhibited intact Leydig cell 3β-HSD with an IC50 of 146.1±0.9μM and 17β-HSD3 with an IC50 of 194.8±1.0μM. The inhibitions of 3β-HSD and 17β-HSD3 by PFOA were competitive for the substrates. In conclusion, PFOA inhibits 3β-HSD and 17β-HSD3 in rat Leydig cells. [Copyright &y& Elsevier]

Phthalates, the most abundantly produced plasticizers, leach out from polyvinyl chloride plastics and disrupt androgen action. Male rats that are exposed to phthalates in utero develop symptoms characteristic of the human condition referred to as testicular dysgenesis syndrome (TDS). Environmental influences have been suspected to contribute to the increasing incidence of TDS in humans (i.e. cryptorchidism and hypospadias in newborn boys and testicular cancer and reduced sperm quality in adult males). In this review, we discuss the recent findings that prenatal exposure to phthalates affects Leydig cell function in the postnatal testis. This review also focuses on the recent progress in our understanding of how Leydig cell factors contribute to phthalate-mediated TDS. [Copyright &y& Elsevier]

Beilong virus (BeiV), a member of the newly recognized genus Jeilongvirus of family Paramyxoviridae , has been reported with limited geographic and host scopes, only in Hongkong, China and from two rat species. Here, by next-generation sequencing (NGS) on dominant wild small animal species in 4 provinces in China, we obtained a complete sequence of BeiV strain from Rattus norvegicus in Guangdong, neighboring HongKong, China. We then made an expanded epidemiological investigation in 11 provinces to obtain the geographic distribution and genetic features of this virus. Altogether 7168 samples from 2005 animals (1903 rodents, 100 shrews, 2 mustelidaes) that belonged to 33 species of Cricetidae, Muridae, Sciuridae and Dipodidae family of Rodentia , 3 species of Soricidae family of Soricomorpha , 2 species of Mustelidae family of Carnivora were examined by RT-PCR and sequencing. A positive rate of 3.7% (266/7168) was obtained that was detected from 22 animal species, including 5 species of Cricetidae family, 12 species of Muridae family, 2 species of Sciuridae family and 3 species of Soricidae family. Phylogenetic analyses based on 154 partial Large gene sequences grouped the current BeiV into two lineages, that were related to their geographic regions and animal hosts. Our study showed the wide distribution of BeiV in common species of wild rodents and shrews in China, highlighting the necessity of epidemiological study in wider regions. • The largest sample size for the detection of BeiV. • A complete sequence of BeiV strain from Rattus. norvegicus in Guangdong. • The epidemiological distribution and genetic features of BeiV by Next-generation sequencing and RT-PCR. • BeiV of genetic diversity was correlated with its geographic origins and wild rodent hosts. [ABSTRACT FROM AUTHOR]